Monitoring impacts from Council Regulation (EU) No 333/2011: End-of-waste criteria for Al/Fe scrap

On 9 October 2011, Council Regulation 333/2011 came into force establishing criteria by which scrap from iron and steel, aluminium and aluminium alloys could cease to be regulated as waste. This study examines the impacts of the Regulation on scrap availability, trade flows, prices, administrative requirements and environment or human health incidents. Because no data currently distinguishes between waste and end-of-waste compliant scrap, information was collected from the EU Competent Authorities and industry using detailed surveys. Across Europe, approximately 250 companies provided responses to the industry survey (representing approximately one quarter of the membership of the scrap industry associations), with a further 15 submissions from industry associations and 25 from Competent Authorities, although the survey responses were notably skewed towards Italy. The results of the study show that more than 1,100 scrap industry companies are already using the end-of-waste criteria across Europe. Uptake is most pronounced in Italy, where over 1,000 scrap companies generate end-of-waste compliant scrap. This rapid uptake in Italy is due in part to a specific legal framework on secondary raw materials already in place before the introduction of the end-of-waste criteria. In the rest of Europe there are a further 100 scrap companies active in end-of-waste scrap. In terms of the quantity of end-of-waste compliant scrap available on the market, this study estimates that, as a lower bound, at least 15% of EU scrap steel and 10% of EU scrap aluminium is compliant. Importantly, this study has found almost no evidence that end-of-waste has caused any negative impacts on the market, whether that be to scrap quality, availability/trade or on the environment. On the contrary, quite a number of the survey participants, both from industry and Competent Authorities highlighted the perceived benefits of the introduction of end-of-waste for metal scrap. These perceived benefits include: creating a simplified regulatory framework and offering companies greater flexibility and legal certainty. Some companies identified improved scrap quality and increased sales prices. At the expert workshop participants debated several ideas for a future monitoring system. One key conclusion was that there is no urgent need to revisit monitoring in the near future, due to the relatively modest rate of uptake outside Italy and the very few, if any, negative impacts observed so far. A repeat of the industry and authorities’ surveys in 2-3 years times was deemed to be the most appropriate way to monitor end-of-waste for scrap metal, and copper scrap could be added to the scope of that exercise.JRC.J.5-Sustainable Production and Consumptio

Unfair Trading Practice Regulation and Voluntary Agreements targeting food waste: A policy assessment in select EU Member States

This report provides a qualitative assessment of Voluntary Agreements (VAs) and Unfair Trading Practices (UTPs) as two typologies of policy interventions having an impact on food loss and waste. To carry out this assessment, two sets of country-based comparative case studies were developed, namely in the UK and Italy for regulations against UTPs, and in the UK and the Netherlands for VAs. The report found that, for both VAs and regulations against UTPs, a preliminary assessment of underlying food supply chain market structure is important to identify the most appropriate policy measures for a specific EU MS (e.g. the size and number of actors at each level of the food supply chain, the level of market concentration and power imbalance among actors, etc.). Specifically concerning UTPs, the following was identified: - Food supply chains are particularly susceptible to UTPs in MS where market power is concentrated within a few large retailers interacting with many suppliers. Perishable products, such as fresh fruits and vegetables supplied direct from primary producers to retailers are particularly at risk due to the time constraints in finding alternate outlets; - It is important to identify solutions for food surplus generated by UTPs (ex: redistributing surplus that results from order cancellations linked to UTPs or ensuring that the \u201cwrongdoer\u201d assumes the responsibility of the food product resulting from the UTPs); - To tackle UTPs, it was found that an effective approach would be the creation of an independent authority to investigate any infringement of good trading practices, (ex: through an industry code of practice, and, if needed, the introduction of sanctions on actors who are found to have not met the standard required by the industry code; - Other recommendations identified include adopting a common EU-level definition of UTPs in relation to grocery supply to avoid unequal treatment of comparable situations across EU, and to allow the judgement of cases based on the principle of equity. Furthermore, indirect and foreign suppliers also need to be protected against UTPs. Specifically concerning VAs the following was identified: - The level and the nature of funding has a significant impact on their lifetime and agendas (a mix of public and private is optimal); - To ensure a VA\u2019s relevance, signatories must benefit from their participating, either financially or in terms of heightened visibility; - VAs should establish ambitious yet realistic targets, achievable by their signatories, and robustness and transparency of data reporting should be forefront to ensure the credibility of the initiatives; - VAs can be implemented alongside compulsory legislation or provide an alternative to it. An advantage of them, compared to legislation, is that they can be designed and adapted relatively quickly depending on political goals related to food waste; - The role of a third party is crucial in managing a VA, notably to facilitate actor accession to it, ensure confidentiality of data, supervise and eventually nudge compliance with the agreement. The report ultimately shows that VAs and UTPs interlinked as VAs can be an effective tool to explore the effects of regulation against UTPs and assess actors\u2019 readiness to avoid market power abuse

Melphalan modifies the bone microenvironment by enhancing osteoclast formation

Melphalan is a cytotoxic chemotherapy used to treat patients with multiple myeloma (MM). Bone resorption by osteoclasts, by remodeling the bone surface, can reactivate dormant MM cells held in the endosteal niche to promote tumor development. Dormant MM cells can be reactivated after melphalan treatment; however, it is unclear whether melphalan treatment increases osteoclast formation to modify the endosteal niche. Melphalan treatment of mice for 14 days decreased bone volume and the endosteal bone surface, and this was associated with increases in osteoclast numbers. Bone marrow cells (BMC) from melphalan-treated mice formed more osteoclasts than BMCs from vehicle-treated mice, suggesting that osteoclast progenitors were increased. Melphalan also increased osteoclast formation in BMCs and RAW264.7 cells in vitro, which was prevented with the cell stress response (CSR) inhibitor KNK437. Melphalan also increased expression of the osteoclast regulator the microphthalmia-associated transcription factor (MITF), but not nuclear factor of activated T cells 1 (NFATc1). Melphalan increased expression of MITF-dependent cell fusion factors, dendritic cell-specific transmembrane protein (Dc-stamp) and osteoclast-stimulatory transmembrane protein (Oc-stamp) and increased cell fusion. Expression of osteoclast stimulator receptor activator of NFκB ligand (RANKL) was unaffected by melphalan treatment. These data suggest that melphalan stimulates osteoclast formation by increasing osteoclast progenitor recruitment and differentiation in a CSR-dependent manner. Melphalan-induced osteoclast formation is associated with bone loss and reduced endosteal bone surface. As well as affecting bone structure this may contribute to dormant tumor cell activation, which has implications for how melphalan is used to treat patients with MM

Systems maps and analytical framework. Mapping food waste drivers across the food supply chain

This report generated 17 systems maps for five contrasting product types that were investigated along their supply chains. The system maps identify: (1) Product specific drivers: drivers specific to the selected food products at a specific stage of the supply chain); (2) Generic drivers: drivers which concern two or more selected products (e.g. labelling errors, limited shelf life etc.); (3) Systemic drivers: drivers that are interlinked with more than one step of the supply chain (e.g. minimum orders, last minute cancellation, lack of data and communication, minimum life on receipt criteria etc.). The cross cutting systemic drivers emphasized supply chain issues, e.g. regarding notably the interactions between the different businesses and unfair trading practices. The systems map approach also shed light on two key factors that impact drivers according to the product specificity: (1) Impacts of food waste drivers highly depend on the level of perishability and microbiological risk of food products. For example, less perishable food products such as frozen and canned products are more likely to be wasted because of product damage, labelling errors and/or equipment breakdown. More perishable and higher risk food products are more likely to be wasted when approaching the \u201cbest before\u201d date or because of supply and demand imbalances and poor information sharing along the supply chain. (2) Lack of communication and cooperation is a central drivers of food waste. The impacts of these are higher in more complex products/supply chains where trouble with one ingredient affects the whole product (e.g. prepared meals). Finally, the systems mapping shed light on drivers which were \u201chiding\u201d behind other drivers. For example, the question of date labelling is a well-known cause of waste for perishable products, but very often there are further drivers behind it (e.g. overstocking in the retail sector)

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Loss of tuberous sclerosis complex 2 sensitizes tumors to nelfinavir−bortezomib therapy to intensify endoplasmic reticulum stress-induced cell death

Cancer cells lose homeostatic flexibility because of mutations and dysregulated signaling pathways involved in maintaining homeostasis. Tuberous Sclerosis Complex 1 (TSC1) and TSC2 play a fundamental role in cell homeostasis, where signal transduction through TSC1/TSC2 is often compromised in cancer, leading to aberrant activation of mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 hyperactivation increases the basal level of endoplasmic reticulum (ER) stress via an accumulation of unfolded protein, due to heightened de novo protein translation and repression of autophagy. We exploit this intrinsic vulnerability of tumor cells lacking TSC2, by treating with nelvinavir to further enhance ER stress while inhibiting the proteasome with bortezomib to prevent effective protein removal. We show that TSC2-deficient cells are highly dependent on the proteosomal degradation pathway for survival. Combined treatment with nelfinavir and bortezomib at clinically relevant drug concentrations show synergy in selectively killing TSC2-deficient cells with limited toxicity in control cells. This drug combination inhibited tumor formation in xenograft mouse models and patient-derived cell models of TSC and caused tumor spheroid death in 3D culture. Importantly, 3D culture assays differentiated between the cytostatic effects of the mTORC1 inhibitor, rapamycin, and the cytotoxic effects of the nelfinavir/bortezomib combination. Through RNA sequencing, we determined that nelfinavir and bortezomib tip the balance of ER protein homeostasis of the already ER-stressed TSC2-deficient cells in favor of cell death. These findings have clinical relevance in stratified medicine to treat tumors that have compromised signaling through TSC and are inflexible in their capacity to restore ER homeostasis